Aleutian Disease virus infection of mink will be employed as a model system to investigate mechanisms of viral persistence and lesion development in those diseases where the etiological agent and a substantial host immune response are coincident. The objectives are to develop in vitro propagation systems which will provide virus free of antibody which can be used in biophysical characterization studies. Antibody-free virus will also be utilized in lymphocyte function studies to delineate mechanisms of hypergammaglobulinemia at the cellular level and to determine the possibility of suppressed cellular immunity which may be related to persistence of virus in vivo. The role of humoral and cellular immunity in lesion development will be pursued. The functional capacity of the reticuloendothelial system will be examined in detail. Finally, the possibility of human infection by Aleutian Disease virus will be investigated. The goal of the proposed research is to develop an understanding of the mechanisms by which a viral agent can induce an excessive antibody response, persist in host tissues, and initiate the lesions seen in Aleutian Disease.